Large numbers of patients with advanced heart disease undergo anesthesia and surgery each year. Although the potent inhalational anesthetics such as halothane, enflurane, and isoflurane afford precise control of anesthetic depth and relatively rapid recovery, their use in these patients may be associated with inordinate depression of cardiac function. The mechanisms by which these potent anesthetics depress myocardial contractility is incompletely understood and antagonism of this depression is not satisfactorily accomplished with the presently available positive inotropic drugs. The scientific goal of the presently proposed research is to obtain an increased understanding of the mechanisms underlying anesthetic-induced depression of myocardial contractility. This is to be accomplished through a systematic study, in isolated intact myocardial tissue, of the effects of anesthetics on the subcellular physiologic processes which promote contraction and relaxation in the heart. A specific aim is to study the effects of anesthetics on the sources of the calcium ions which activate the contractile process. In particular, the way in which anesthetics affect calcium movements as well as the way in which these agents alter the internal cellular storage and release of calcium will be studied. Calcium ion selective microelectrodes will be employed to evaluate the effects of anesthetics on calcium movement into and out of the cell. Potentiated state contractions and rapid cooling contractures will be used to study anesthetic effects on cellular storage and release processes. Electron probe X-ray microanalysis will be used to determine the cellular content and location of calcium and the way in which these are affected by anesthetics. It is proposed that an increased understanding of the mechanisms which underlie anesthetic depression of myocardial contractility will facilitate rational methods for its reversal.